POS1329 DESIGN OF A PHASE III, RANDOMISED, PLACEBO-CONTROLLED TRIAL OF BI 1015550 IN PATIENTS WITH PROGRESSIVE FIBROSING INTERSTITIAL LUNG DISEASE
Authors: T. Maher, S. Assassi, A. Azuma, V. Cottin, A. M. Hoffmann-Vold, M. Kreuter, J. Oldham, L. Richeldi, C. Valenzuela, M. Wijsenbeek, C. Coeck, F. Voss, D. Wachtlin, F. Martinez
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF), and occurs in a range of disorders such as connective tissue diseases or hypersensitivity pneumonitis. Patients with PPF have comparable disease progression, lung function decline and mortality as patients with IPF. It is therefore hypothesised that they share underlying pathobiology and may respond to the same treatments, as was also seen in the Phase III INBUILD trial of nintedanib. BI 1015550, a preferential phosphodiesterase 4B inhibitor, prevented lung function decline in a Phase II study in IPF and may provide an additional treatment option, alone or with nintedanib, in patients with PPF. <h3>Objectives</h3> This Phase III trial (FIBRONEER-ILD<sup>™</sup>) will investigate the efficacy and safety of BI 1015550 in patients with PPF. <h3>Methods</h3> This double-blind, randomised, placebo-controlled trial (NCT05321082) is underway at approximately 400 sites in 45 countries. It is planned that 1041 patients will be randomised in a 1:1:1 ratio to either 18 mg BI 1015550 twice daily (BID), 9 mg BI 1015550 BID or placebo, in addition to standard of care, over at least 52 weeks (Figure 1). Similar to the INBUILD trial, patients are stratified by high-resolution computed tomography pattern (usual interstitial pneumonia-like vs other fibrotic patterns), and by baseline use of nintedanib (yes/no). Patients are enrolled if they meet the predefined criteria for PPF and other criteria (Table 1). <h3>Results</h3> The trial initiated and began enrolment in October 2022. Enrolment is expected to complete by the end of 2023. The primary endpoint is absolute change from baseline in forced vital capacity (FVC) (mL) at Week 52. The key secondary endpoint is the time to first acute exacerbation, first hospitalisation for respiratory cause or death (whichever occurs first) over the duration of the trial. <h3>Conclusion</h3> The FIBRONEER-ILD™ trial is designed to investigate the potential use of BI 1015550 as a treatment option for patients with PPF, with and without background nintedanib treatment. <h3>Acknowledgements</h3> This study was supported and funded by Boehringer Ingelheim International GmbH (BI). The author did not receive payment for the development of the abstract. Eleni Tzouramani, MSc, of Meditech Media provided writing, editorial support and formatting assistance, which was contracted and funded by BI. BI was given the opportunity to review the abstract for medical and scientific accuracy as well as intellectual property considerations. <h3>Disclosure of Interests</h3> Toby Maher Speakers bureau: Boehringer Ingelheim; Roche/Genentech, Paid instructor for: Boehringer Ingelheim; Roche/Genentech, Consultant of: Personal payment from: AstraZeneca, Bayer, Blade Therapeutics, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant, Respivant, Theravance, Veracyte., Shervin Assassi Consultant of: Novartis; Boehringer Ingelheim; AstraZeneca; CSL Behring; Abbvie, Grant/research support from: Boehringer Ingelheim; Janssen, Arata Azuma Speakers bureau: Boehringer Ingelheim; Taiho Pharm. Co., Consultant of: Boehringer Ingelheim; Taiho Pharm. Co.; Toray Medical Co.; Kyorin Pharm. Co., Grant/research support from: Boehringer Ingelheim; Taiho Pharm. Co, Vincent Cottin Speakers bureau: Boehringer Ingelheim; Roche, Consultant of: Boehringer Ingelheim; Roche; Galapagos; Shionogi; RedX; Pure Tech; Celgene/BMS; AstraZeneca; CSL Behring; Sanofi, Grant/research support from: Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion; ARXX; Bayer; Boehringer-Ingelheim; Janssen; Lilly; Medscape; Merck Sharp &amp; Dohme; Roche, Consultant of: Actelion; ARXX; Bayer; Boehringer Ingelheim; Janssen; Medscape; Roche, Grant/research support from: Boehringer Ingelheim; Janssen, Michael Kreuter Speakers bureau: Boehringer Ingelheim; Galapagos; Roche, Consultant of: Boehringer Ingelheim; Galapagos; Roche, Grant/research support from: Boehringer Ingelheim; Roche, Justin Oldham Consultant of: Boehringer Ingelheim; Roche/Genentech; Lupin Pharmaceuticals, Grant/research support from: Boehringer Ingelheim, Luca Richeldi Speakers bureau: Boehringer Ingelheim; Zambon; Cipla; Roche, Consultant of: Biogen; Celgene; Nitto; Pliant Therapeutics; Toray; BMS; RespiVant; CSL Behring; Roche; Boehringer Ingelheim; FibroGen; Promedior, Grant/research support from: Boehringer Ingelheim; Italian Drug Agency, CLAUDIA VALENZUELA Speakers bureau: Boehringer Ingelheim; Hoffmann-La Roche, Ltd; BMS, Consultant of: Boehringer Ingelheim; Hoffmann-La Roche, Ltd; BMS, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim; Hoffman la Roche; Novartis; CLS Behring; Galapagos, Consultant of: Boehringer Ingelheim; Hoffman la Roche; Galapagos; Bristol Myers Squibb; Galecto; Respivant; Nerretherapeutics; Horizontherapeutics; PureTech health; Kinevant Sciences; Molecure; CLS Behring; Thyron; Vicore; Savara; Galapagos, Grant/research support from: Boehringer Ingelheim; Hoffman la Roche; The Netherlands Organisation for Health Research and Development; The Dutch Lung Foundation; The Dutch Pulmonary Fibrosis; AstraZeneca-Daiichi, Carl Coeck Employee of: Boehringer Ingelheim Pharmaceuticals, Inc, Florian Voss Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., Daniel Wachtlin Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., Fernando Martinez Consultant of: AbbVie; Boehringer Ingelheim; Bristol-Myers Squibb; Bridge Biotherapeutics; CSL Behring; DevPro; IQVIA; Roche/Genentech; Sanofi; Shionogi; twoXAR; United Therapeutics; Veracyte; Afferent/Merck; Bayer; Biogen; Nitto; Respivant; Roche.